Taste (gustatory) cells are defined by their ability to detect water-soluble chemical cues and to convey this information to higher processing centers in the brain. The molecular mechanisms underlying this process are not completely understood. C. elegans has a simple nervous system that contains few chemosensory neurons, yet produces behavioral responses to numerous chemical cues. The simple neuroanatomy and genetic amenability of this organism make it a powerful model system for the study of the molecular determinants of taste responsiveness. A striking feature of the C. elegans chemosensory system is that several salts are sensed in a left/right asymmetric manner in the bilateral ASE gustatory neuron pair. This correlates with asymmetric gene expression profiles of receptor-type guanylyl cyclases, a putative class of chemoreceptor proteins. The main aims of this study include the following: (1) Characterize the spectrum of chemicals the ASE neurons respond to and determine how many of these are sensed in an asymmetric manner. This will be accomplished by testing the responsiveness of mutant animals in which only the left or right ASE cell fate develops to a panel of known and novel taste cues. (2) Examine the involvement of the putative chemoreceptors encoded by the guanylyl cyclase (gcy) gene family, using loss-of-function and gain-of- function genetic modifications. (3) Determine if other classes of putative chemoreceptors are required for the behavioral taste response, with a focus on possible salt chemoreceptors. Specifically, mutants lacking expression of transient receptor potential (TRP) channels and amiloride-sensitive epithelial sodium channels (ENaC/degenerins) will be tested in sensitive behavioral assays for salt chemotaxis defects. The identification of salt taste receptors in nematodes will provide important genetic evidence that related receptors in humans also play a role in salt detection. This information could be useful in the development of synthetic flavor enhancers that could be of clinical value for patients whose conditions require salt- restricted diets. Furthermore, analysis of the lateralization of chemosensory receptors in C. elegans taste neurons could reveal a mechanism that may be used by higher organisms to achieve the ability to respond to the multitude of taste and odorant molecules they encounter.